The working hypothesis of this proposal is that certain forms of learning reflect changes in the strengths of synaptic connections between the critically-involved neurons. The synaptic hypothesis for learning has not yet been adequately tested in mammals, although there is plenty of indirect evidence. The phenomenon of long-term synaptic potentiation (LTP), first discovered in the hippocampus, is widely touted as the most promising candidate synaptic substrate for rapid forms of learning In vertebrates. LTP was recently discovered to occur in the amygdala, another temporal lobe brain structure. The amygdala and hippocampus have repeatedly been implicated in various mnemonic functions in man and other animals. Knowledge of the cellular neurophysiology of the hippocampus and the mechanisms underlying hippocampal LTP is beginning to emerge, but comparable information does not exist for the amygdala. The goal of this proposal is to understand the mechanisms underlying amygdaloid LTP at the level of cellular neurophysiology and to test the idea that this form of synaptic plasticity is in fact involved in a particular type of rapid Pavlovian conditioning. The mechanisms will be explored using cultured and acute amygdala brain slices (two preparations that this laboratory has been developing) in conjunction with high-resolution visualization and neurophysiological techniques (whose application to brain slices this laboratory has also helped to pioneer). The knowledge gained from these in vitro systems about the underlying mechanisms will be used in in vivo experiments designed to test the hypothesis that amygdaloid LTP participates in aspects of rapid fear conditioning. The information that will be provided is relevant not only to the synaptic hypothesis for learning. The amygdala has major significance for neurology and psychiatry. Further understanding of the cellular neurophysiology and pharmacology of this structure will be relevant to the cause or treatment of numerous human neuropsychological disorders--possibly including major and minor mood disorders, memory impairments, sexual dysfunctions, epilepsy and certain violent behaviors.